Creation of AlkB Mutants for Protection of Bone Marrow
创建用于保护骨髓的 AlkB 突变体
基本信息
- 批准号:7253993
- 负责人:
- 金额:$ 13.25万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2006
- 资助国家:美国
- 起止时间:2006-07-01 至 2011-06-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAdenineAdverse effectsAlkylating AgentsAlkylationAllelesAnimal ModelBacteriophage M13Base Excision RepairsBase PairingBiological AssayBloodBlood CellsBone MarrowBone Marrow SuppressionBrain NeoplasmsBypassCampingCarmustineCatalysisCell LineCellsChargeClinicClinicalClinical TrialsCollaborationsCoupledDNADNA AdductsDNA Modification ProcessDacarbazineDoseDose-LimitingEnzymesEscherichia coliEvolutionExcisionFigs - dietaryGenerationsGenesGenetic MaterialsGenomicsGoalsGuanineHematopoieticHemorrhageHomologous GeneHumanHuman Cell LineInfectionInsectaLesionLibrariesLymphomaMammalian CellMarrowMediatingMethylationModelingModificationMusMutagenesisMutationNitrogenO(6)-Methylguanine-DNA MethyltransferasePerformancePharmaceutical PreparationsPositioning AttributeProcarbazinePropertyProteinsPurinesPyrimidinePyrimidinesReactionRelative (related person)ResistanceSingle-Stranded DNASiteSoft Tissue NeoplasmsSolidStem cellsSubstrate SpecificitySuicideSystemTestingToxic effectTrainingTranslationsUniversitiesVariantVascular blood supplyVeterinariansWashingtonWorkadductbasecancer therapyclinically relevantcomparativecytotoxiccytotoxicitydesigndirected evolutionds-DNAenzyme pathwaygene therapyimprovedin vivokillingslexitropsinmelanomamethyl groupmethyl lexitropsinmethylpurinemouse modelmutantneoplastic cellpreferenceprotective effectpurinerepairedtemozolomidetissue culture
项目摘要
DESCRIPTION (provided by applicant): Methylating agents are mainstay drugs for the treatment of cancer and are amongst the few agents available against brain tumors.
Cells responsible for keeping the blood cell supply, "blood progenitor cells", are highly sensitive to these agents, which results in severe side-effects, including bleeding and infection.
Blood progenitor cells can be protected from the toxic effects of methylation by resistance genes. The most effective one is AGT, which directly removes toxic modifications caused by methylation of the cell's genetic material (DNA). However, AGT does not recognize certain toxic DNA modifications. Here I propose the use of a different gene (AlkB), which targets some of these alternative lesions, to improve protection against the toxic effects of methylation. This gene, which has only recently been characterized, should therefore enhance AGT protection. Moreover, unlike AGT, AlkB remains active after mediating a repair reaction, which implies that AlkB repair should be more amenable to modulation.
Here I propose a powerful approach to identify variants of one human homologue of AlkB (ABH2) with improved repair performance. Specifically, I want to enhance the enzyme's ability to recognize lesions generated by agents used in the clinic. Selected variants will be tested in human progenitor cells in culture and in a mouse animal model for protection against treatment with high doses of these agents. Ultimately, the mutants identified in this work should improve the management of side effects of methylating agents and would also allow the use of higher doses for more effective treatment.
描述(由申请人提供):甲基化药物是治疗癌症的主要药物,也是治疗脑肿瘤的少数药物之一。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Manel Camps其他文献
Manel Camps的其他文献
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{{ truncateString('Manel Camps', 18)}}的其他基金
Mechanisms of selective excision and oxidative repair of alkylated DNA
烷基化DNA的选择性切除和氧化修复机制
- 批准号:
8187771 - 财政年份:2011
- 资助金额:
$ 13.25万 - 项目类别:
Mechanisms of selective excision and oxidative repair of alkylated DNA
烷基化DNA的选择性切除和氧化修复机制
- 批准号:
8478102 - 财政年份:2011
- 资助金额:
$ 13.25万 - 项目类别:
Mechanisms of selective excision and oxidative repair of alkylated DNA
烷基化DNA的选择性切除和氧化修复机制
- 批准号:
8306937 - 财政年份:2011
- 资助金额:
$ 13.25万 - 项目类别:
Mechanisms of selective excision and oxidative repair of alkylated DNA
烷基化DNA的选择性切除和氧化修复机制
- 批准号:
8878258 - 财政年份:2011
- 资助金额:
$ 13.25万 - 项目类别:
Mechanisms of selective excision and oxidative repair of alkylated DNA
烷基化DNA的选择性切除和氧化修复机制
- 批准号:
8691813 - 财政年份:2011
- 资助金额:
$ 13.25万 - 项目类别:
Creation of AlkB Mutants for Protection of Bone Marrow
创建用于保护骨髓的 AlkB 突变体
- 批准号:
7858430 - 财政年份:2006
- 资助金额:
$ 13.25万 - 项目类别:
Creation of AlkB Mutants for Protection of Bone Marrow
创建用于保护骨髓的 AlkB 突变体
- 批准号:
7626726 - 财政年份:2006
- 资助金额:
$ 13.25万 - 项目类别:
Creation of AlkB Mutants for Protection of Bone Marrow
创建用于保护骨髓的 AlkB 突变体
- 批准号:
7088584 - 财政年份:2006
- 资助金额:
$ 13.25万 - 项目类别:
Creation of AlkB Mutants for Protection of Bone Marrow
创建用于保护骨髓的 AlkB 突变体
- 批准号:
7463139 - 财政年份:2006
- 资助金额:
$ 13.25万 - 项目类别:
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